Targeting glutamine metabolism exhibits anti-tumor effects in thyroid cancer.

BACKGROUND: Effective treatment for patients with advanced thyroid cancer is lacking. Metabolism reprogramming is required for cancer to undergo oncogenic transformation and rapid tumorigenic growth. Glutamine is frequently used by cancer cells for active bioenergetic and biosynthetic needs. This study aims to investigate whether targeting glutamine metabolism is a promising therapeutic strategy for thyroid cancer. METHODS: The expression of glutaminase (GLS) and glutamate dehydrogenase (GDH) in thyroid cancer tissues was evaluated by immunohistochemistry, and glutamine metabolism-related genes were assessed using real time-qPCR and western blotting. The effects of glutamine metabolism inhibitor 6-diazo-5-oxo-l-norleucine (DON) on thyroid cancer cells were determined by CCK-8, clone formation assay, Edu incorporation assay, flow cytometry, and Transwell assay. The mechanistic study was performed by real time-qPCR, western blotting, Seahorse assay, and gas chromatography-mass spectrometer assay. The effect of DON prodrug (JHU-083) on thyroid cancer in vivo was assessed using xenograft tumor models in BALB/c nude mice. RESULTS: GLS and GDH were over-expressed in thyroid cancer tissues, and GLS expression was positively associated with lymph-node metastasis and TNM stage. The growth of thyroid cancer cells was significantly inhibited when cultured in glutamine-free medium. Targeting glutamine metabolism with DON inhibited the proliferation of thyroid cancer cells. DON treatment did not promote apoptosis, but increased the proportion of cells in the S phase, accompanied by the decreased expression of cyclin-dependent kinase 2 and cyclin A. DON treatment also significantly inhibited the migration and invasion of thyroid cancer cells by reducing the expression of N-cadherin, Vimentin, matrix metalloproteinase-2, and matrix metalloproteinase-9. Non-essential amino acids, including proline, alanine, aspartate, asparagine, and glycine, were reduced in thyroid cancer cells treated with DON, which could explain the decrease of proteins involved in migration, invasion, and cell cycle. The efficacy and safety of DON prodrug (JHU-083) for thyroid cancer treatment were verified in a mouse model. In addition to suppressing the proliferation and metastasis potential of thyroid cancer in vivo, enhanced innate immune response was also observed in JHU-083-treated xenograft tumors as a result of decreased expression of cluster of differentiation 47 and programmed cell death ligand 1. CONCLUSIONS: Thyroid cancer exhibited enhanced glutamine metabolism, as evidenced by the glutamine dependence of thyroid cancer cells and high expression of multiple glutamine metabolism-related genes. Targeting glutamine metabolism with DON prodrug could be a promising therapeutic option for advanced thyroid cancer.

[Artificial intelligence research advances in discrimination and diagnosis of pulmonary ground-glass nodules].

Lung cancer, which accounts for about 18% of all cancer-related deaths worldwide, has a dismal 5-year survival rate of less than 20%. Survival rates for early-stage lung cancers (stages IA1, IA2, IA3, and IB, according to the TNM staging system) are significantly higher, underscoring the critical importance of early detection, diagnosis, and treatment. Ground-glass nodules (GGNs), which are commonly seen on lung imaging, can be indicative of both benign and malignant lesions. For clinicians, accurately characterizing GGNs and choosing the right management strategies present significant challenges. Artificial intelligence (AI), specifically deep learning algorithms, has shown promise in the evaluation of GGNs by analyzing complex imaging data and predicting the nature of GGNs, including their benign or malignant status, pathological subtypes, and genetic mutations such as epidermal growth factor receptor (EGFR) mutations. By integrating imaging features and clinical data, AI models have demonstrated high accuracy in distinguishing between benign and malignant GGNs and in predicting specific pathological subtypes. In addition, AI has shown promise in predicting genetic mutations such as EGFR mutations, which are critical for personalized treatment decisions in lung cancer. While AI offers significant potential to improve the accuracy and efficiency of GGN assessment, challenges remain, such as the need for extensive validation studies, standardization of imaging protocols, and improving the interpretability of AI algorithms. In summary, AI has the potential to revolutionise the management of GGNs by providing clinicians with more accurate and timely information for diagnosis and treatment decisions. However, further research and validation are needed to fully realize the benefits of AI in clinical practice.

[Research progress on the application of non-nutritional effects of fat emulsion in the treatment of poisoning].

Fat emulsion is a drug commonly used clinically for parenteral nutrition support in critically ill patients.With the development of the pharmaceutical industry, fat emulsion has formed a variety of different formulations, among which different types of fat emulsion have their own metabolic and body energy supply characteristics, and the application indications are also different. In addition to providing the supply of nutrients, the role of fat emulsion in anti-toxicity, immune regulation, anti-inflammatory, anti-shock, cardiopulmonary resuscitation and other aspects has gradually been discovered. This article reviews the existing evidence-based medical evidence and expounds the mechanism and therapeutic role of fat emulsion in the treatment of critically ill patients with poisoning. Its value in the treatment of critically ill patients with poisoning was discussed, and some references were provided for the application of non-nutritional functions of fat emulsion in the future.

Imaging gate-tunable Tomonaga-Luttinger liquids in 1H-MoSe2 mirror twin boundaries.

One-dimensional electron systems exhibit fundamentally different properties than higher-dimensional systems. For example, electron-electron interactions in one-dimensional electron systems have been predicted to induce Tomonaga-Luttinger liquid behaviour. Naturally occurring grain boundaries in single-layer transition metal dichalcogenides exhibit one-dimensional conducting channels that have been proposed to host Tomonaga-Luttinger liquids, but charge density wave physics has also been suggested to explain their behaviour. Clear identification of the electronic ground state of this system has been hampered by an inability to electrostatically gate such boundaries and tune their charge carrier concentration. Here we present a scanning tunnelling microscopy and spectroscopy study of gate-tunable mirror twin boundaries in single-layer 1H-MoSe2 devices. Gating enables scanning tunnelling microscopy and spectroscopy for different mirror twin boundary electron densities, thus allowing precise characterization of electron-electron interaction effects. Visualization of the resulting mirror twin boundary electronic structure allows unambiguous identification of collective density wave excitations having two velocities, in quantitative agreement with the spin-charge separation predicted by finite-length Tomonaga-Luttinger liquid theory.

Discovery of intrinsic ferromagnetism in two-dimensional van der Waals crystals.

The realization of long-range ferromagnetic order in two-dimensional van der Waals crystals, combined with their rich electronic and optical properties, could lead to new magnetic, magnetoelectric and magneto-optic applications. In two-dimensional systems, the long-range magnetic order is strongly suppressed by thermal fluctuations, according to the Mermin-Wagner theorem; however, these thermal fluctuations can be counteracted by magnetic anisotropy. Previous efforts, based on defect and composition engineering, or the proximity effect, introduced magnetic responses only locally or extrinsically. Here we report intrinsic long-range ferromagnetic order in pristine Cr2Ge2Te6 atomic layers, as revealed by scanning magneto-optic Kerr microscopy. In this magnetically soft, two-dimensional van der Waals ferromagnet, we achieve unprecedented control of the transition temperature (between ferromagnetic and paramagnetic states) using very small fields (smaller than 0.3 tesla). This result is in contrast to the insensitivity of the transition temperature to magnetic fields in the three-dimensional regime. We found that the small applied field leads to an effective anisotropy that is much greater than the near-zero magnetocrystalline anisotropy, opening up a large spin-wave excitation gap. We explain the observed phenomenon using renormalized spin-wave theory and conclude that the unusual field dependence of the transition temperature is a hallmark of soft, two-dimensional ferromagnetic van der Waals crystals. Cr2Ge2Te6 is a nearly ideal two-dimensional Heisenberg ferromagnet and so will be useful for studying fundamental spin behaviours, opening the door to exploring new applications such as ultra-compact spintronics.

Deep learning for predicting the risk of immune checkpoint inhibitor-related pneumonitis in lung cancer.

AIM: To develop and validate a nomogram model that combines computed tomography (CT)-based radiological factors extracted from deep-learning and clinical factors for the early predictions of immune checkpoint inhibitor-related pneumonitis (ICI-P). MATERIALS AND METHODS: Forty ICI-P patients and 101 patients without ICI-P were divided randomly into the training (n=113) and test (n=28) sets. The convolution neural network (CNN) algorithm was used to extract the CT-based radiological features of predictable ICI-P and calculated the CT score of each patient. A nomogram model to predict the risk of ICI-P was developed by logistic regression. RESULTS: CT score was calculated from five radiological features extracted by the residual neural network-50-V2 with feature pyramid networks. Four predictors of ICI-P in the nomogram model included a clinical feature (pre-existing lung diseases), two serum markers (absolute lymphocyte count and lactate dehydrogenase), and a CT score. The area under curve of the nomogram model in the training (0.910 versus 0.871 versus 0.778) and test (0.900 versus 0.856 versus 0.869) sets was better than the radiological and clinical models. The nomogram model showed good consistency and better clinical practicability. CONCLUSION: The nomogram model that combined CT-based radiological factors and clinical factors can be used as a new non-invasive tool for the early prediction of ICI-P in lung cancer patients after immunotherapy with low cost and low manual input.

[Effect of high flow nasal catheter oxygen to prevent hypoxemia in endoscopic retrograde cholangiopancreatography surgery in aged].

Objective: To explore the effect of high-flow nasal catheter oxygen inhalation in preventing hypoxemia during endoscopic retrograde cholangiopancreatography (ERCP) surgery in elderly patients. Methods: From September 2021 to September 2022, 116 elderly patients (aged ≥ 70 years) who underwent elective ERCP in the Northern Theater General Hospital were prospectively selected, then divided into general nasal catheter oxygen inhalation group [group C, 31 males and 27 females, aged (79.8±6.4) years] and high-flow nasal catheter oxygen inhalation group [group H, 33 males and 25 females, aged (81.4±6.7) years], with 58 patients in each group. All patients were monitored for anesthesia by target-controlled infusion of propofol and remifentanil. The main outcome index was the incidence of intraoperative subclinical hypoxemia (90% ≤ SpO2 < 95%, duration >5 s), hypoxemia (75% < SpO2 < 90%, 5 s < duration ≤ 60 s) and severe hypoxemia (SpO2 < 75% or SpO2 < 90%, duration > 60 s). Secondary observation measures were SpO2 from T0 to T5 (T0, before anesthesia induction; T1, immediately after anesthesia induction; T2, endoscopic introduction; T3, duodenal papula intubation; T4, endoscopic withdrawal; T5, postoperative awakening), the arterial oxygen partial pressure (PaO2), carbon dioxide partial pressure (PaCO2) and pH at T0, 15 min after the induction and T5. Results: The incidence of intraoperative subclinical hypoxemia in group C and group H was 12.0% (7/58) and 3.4% (2/58) respectively, which showed no significant statistical difference (P=0.165) from each other. The incidence of intraoperative hypoxemia in group H was 8.6% (5/58), which was significantly lower than 31.0% (18/58) of group C (P=0.003). Neither group had intraoperative severe hypoxemia. SpO2 of group H were (98.2±0.9)%, (98.2±0.9)%, (97.8±1.7)% and (97.7±1.7)% at T1, T2, T3, T4, which were higher than (96.8±2.1)%, (96.4±3.0)%, (96.1±2.9)% and (96.4±3.4)% in group C (all P<0.05). PaO2 at 15 min after induction in group H was (240.5±46.7) mmHg (1 mmHg=0.133 kPa), which was higher than that of group C (170.6±33.4) mmHg (P<0.001). There was no statistically significant difference in pH and PaCO2 between the two groups of patients at each timepoint. Conclusion: High flow nasal catheter oxygen can effectively reduce the incidence of hypoxemia in ERCP in elderly patients.

[Investigation of diagnostic methods and criteria for gastroesophageal reflux-related cough].

Gastroesophageal reflux-related cough is a multidisciplinary disease that cannot be diagnosed solely based on typical reflux-related symptoms. Its current diagnostic methods and criteria are largely derived from those used for gastroesophageal reflux disease, with slight differences. Esophageal reflux monitoring can provide objective evidence for the diagnosis of gastroesophageal reflux-related cough and is therefore the first-choice of laboratory tests recommended by the guidelines for cough management. Acid exposure time and syndrome association probability have been accepted as the diagnostic criteria, while esophageal motility assessment also has some certain auxiliary diagnostic value. Based on the existing evidence, we have reviewed how to improve the diagnostic methods and criteria for gastroesophageal reflux-related cough, as well as the issues that need to be addressed in the future.

[Esophageal dysmotility detection in patients with gastroesophageal reflux-related cough and its influence on the efficacy of anti-reflux therapy].

Objective: To investigate the characteristics of esophageal dysmotility in patients with an initial diagnosis of acid/non-acid gastroesophageal reflux-related cough (GERC), and its correlation with the therapeutic response to anti-reflux treatments to search for the useful indicators to screen patients with chronic cough suitable for anti-reflux therapy. Methods: A total of 173 patients with suspicious GERC who attended the Chronic Cough Specialist Clinic of Department of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University between June 2020 and December 2022 were retrospectively selected for the study. The age of the patients was (45.1±14.6) years old, including 87 males and 86 females. Their demographic characteristics, clinical manifestations, and the results of high-resolution manometry (HRM) and multichannel intraluminal impedance-pH monitoring (MII-pH) were collected. Information on the etiological identification process and final diagnosis was also recorded. The recruited cases were grouped according to therapeutic outcomes and divided into cases with a favourable response to conventional anti-reflux treatment, cases with a favourable response to intensified anti-reflux treatment, and cases with no response to anti-reflux treatment. Factors influencing the efficacy of anti-reflux treatment were investigated. Differences between groups were compared using the χ2 test, Student-Newman-Keuls test, and Kruskal-Wallis H(K) test, where applicable. Logistic regression analysis using forward stepwise regression based on maximum likelihood estimation was used to screen for influence factors. Results: The 175 patients with suspicious GERC included 45 (26.0%) patients who responded to conventional anti-reflux treatment, 54 (31.2%) who responded to intensified anti-reflux treatment and 74 (42.8%) who did not respond to anti-reflux therapies. Esophageal dysmotility was present in 52.0% of patients (90/173), but was less common in patients who responded to conventional anti-reflux treatment (χ2=8.09, P=0.018). Although the majority of reflux episodes were non-acid (136/173, 78.6%), the proportion of acid reflux (χ2=19.49, P<0.001) and acid exposure time (H=11.04, P=0.004) were significantly higher in patients who responded to conventional anti-reflux treatment. The patients with acid and non-acid GERC had comparable proportion of esophageal dysmotility (64.9% vs. 48.5%, χ2=3.11, P=0.078), with a shorter break [2.4 (0.7, 5.6) cm vs. 6.1 (1.4, 10.0) cm, Z=-2.39, P=0.017], longer upper esophageal sphincter [(4.1±0.9) cm vs. (3.7±1.3) cm, t=-2.09, P=0.038], higher percentage of normal esophageal contractions [60.0% (17.8%, 90.0%) vs. 30.0% (0, 80.0%), Z=-2.14, P=0.032], and lower percentage of large break [10.0% (0, 40.0%) vs. 50.0% (0, 100.0%), Z=-2.92, P=0.004] in the patients with non-acid GERC. The mean resting pressure of the lower esophageal sphincter was significantly lower (H=7.49, P=0.024), while the percentage of ineffective esophageal contractions was markedly higher (H=8.60, P=0.014) in the patients who responded to intensified anti-reflux treatment and in the patients who did not respond to the anti-reflux therapies. Multifactorial logistic regression analysis identified the percentage of ineffective contraction as an independent factor predicting the efficacy of conventional anti-reflux treatment, with a cut-off value of≤45% and a moderate predictive value (AUC=0.67, P=0.004). Conclusions: Esophageal dysmotility is common in GERC patients with different characteristics in acid and non-acid GERC. The percentage of ineffective esophageal contraction may be a useful indicator for selecting an anti-reflux strategy and predicting treatment outcomes.

Comparison of Telomere Length between Buccal Cells and Blood Cells.

Telomere length (TL) in blood cells is commonly used as a proxy for TL in other tissue types. The source of DNA of adequate quality and quantity is important for TL analysis. Compared to blood cells, buccal cells easy for genomic DNA preparation would facilitate the rapid and reliable TL analysis. However, the feasibility of buccal cells for TL analysis remains yet unestablished. We characterized TL of buccal cells and blood cells collected from 52 individuals using buccal cell swabs and fingertip sticks. Relative TL (RTL) determined by quantitative PCR showed that there is a strong correlation between buccal RTL and blood RTL (r=0.877, p<0.001), suggesting that buccal cells are adequate sources of DNA for TL analysis. The validity of sampling using buccal cell swabs provides simple operation and good reproducibility for TL analysis, that overcomes the discomfort and risk of infection caused by blood sampling.

[Diagnosis and treatment of gastroesophageal reflux-related cough: consensus and controversies].

Typical reflux symptoms associated with gastroesophageal reflux-related cough have diagnostic implications. Questionnaires including these symptoms can be used as valuable screening tools for potential candidates. When reflux monitoring provides the objective evidence of abnormal reflux, the favorable response to anti-reflux therapy is essential for the diagnostic confirmation, in which anti-acid drugs are still the first-line choice. The benefits of neuromodulators in the treatment of refractory gastroesophageal reflux-related cough need to be further clarified. However, anti-reflux surgery may be a promising curative therapy for some patients with definitive surgical indications.

[Chronic cough in China: progress and perspectives].

Great progress has been made in regard of mechanism, etiological diagnosis and treatment of chronic cough since the beginning of the 20th century, and Chinese guidelines of diagnosis, management of cough was developed. Moreover, Chinese experts also participated in the formulation of international cough guidelines. Through the promotion of the guidelines, the level of diagnosis and treatment of chronic cough has been significantly improved in China. In the future, we should strengthen the studies on the epidemiology of chronic cough, the central regulation of chronic cough, and the treatment of refractory chronic cough, and promote the cough guidelines in primary community hospitals.

[Accurate understanding of the changes in the recommendations on coronary artery bypass grafting and radial artery in the 2021 ACC/AHA/SCAI Guideline For Coronary Artery Revascularization].

The 2021 ACC/AHA/SCAI Guideline For Coronary Artery Revascularization has been brought into focus and widely questioned by multiple associations of cardiac surgeons around the world, in which the class of recommendation (COR) for coronary artery bypass grafting (CABG) was downgraded from Ⅰ to Ⅱb in the treatment of 3 vessel coronary artery disease, and the use of radial artery as CABG conduit was elevated to COR Ⅰ. The ISCHEMIA trial, which was cited by the guidelines as evidence, had obvious selection bias. It did not consider the advantages of long-term patency rate of CABG in patients with high risk factors, and did not define that radial artery bypass has a certain applicable population. Only by widely collecting and carefully selecting evidence and collaborating with cardiac surgeons in the multidisciplinary team of coronary heart disease, the more reasonable and comprehensive guidelines and suggestions could be formed.

[Clinical analysis of 25 cases of acute oral 84 disinfectant poisoning].

Objective: To summarize the clinical characteristics and treatment effect of patients with acute oral 84 disinfectant poisoning, so as to improve the understanding, diagnosis and treatment of the disease. Methods: In January 2022, 25 hospitalized patients with acute oral 84 disinfectant poisoning admitted to our department from March 2016 to August 2021 were selected as the research objects, and their general conditions, poisoning reasons, poisoning time, dose of poisoning, clinical manifestations, blood routine and biochemical indicators, diagnosis, treatment and prognosis were selected. Results: A retrospective analysis was performed. Among the 25 patients, there were 4 males and 21 females, aged from 20 to 91 years, and M (Q(1), Q(3)) was 38.7 (27, 46) years; The poisoning time (from exposure to poison to treatment) was 1~72 h, and M (Q(1), Q(3)) was 10.5 (3, 11.5) h. The length of stay was 1~20 days, and M (Q(1), Q(3)) was 5.72 (2, 7) days.The dose was 40-500 ml, and the M (Q(1), Q(3)) was 219.6 (100, 330) ml. Chest CT showed exudative changes in both lungs in 4 patients, excessive decreased permeability in 1 case and pleural effusion in 1 case. Gastroscope showed 2 cases of erosive inflammation of gastric body and antrum, 1 case of esophageal ulcer and cardiac ulcer, 1 case of corrosive gastritis, gastric fundus ulcer and esophageal stenosis. Abdominal X-ray showed 1 case of abdominal intestinal dilatation and pneumatosis with multiple gas-liquid planes.There were 1 case of type I respiratory failure, 6 cases of gastrointestinal bleeding and 1 case of incomplete intestinal obstruction. There were 19 cases of nausea and vomiting, 9 cases of abdominal pain, 6 cases of pharyngeal pain and 6 cases of retrosternal burning pain, 1 case of cough and 2 cases of fatigue. Conclusion: Acute oral 84 disinfectant will cause varying degrees of damage to the human digestive tract and lungs. In severe cases, gastrointestinal bleeding, intestinal obstruction, hypoxemia, etc, and even life-threatening, should be paid attention to clinically. The treatment is mainly symptomatic support treatment, such as protecting gastrointestinal mucosa, controlling acute inflammatory reaction, protecting the functions of liver and kidney and other important organs.

Diversity of Botryosphaeriaceae Species Associated with Chinese Hickory Tree (Carya cathayensis) Trunk Cankers.

Tree trunk cankers represent serious fungal diseases that pose significant threats to Chinese hickory trees (Carya cathayensis). To characterize the pathogen diversity associated with this disease, tissues were collected between 2016 and 2018 from the primary Chinese hickory plantation regions. A total of 97 cultures were isolated from trees in six towns (Longgang, Qingliangfeng, Changhua, Tuankou, Taiyang Town, and Lin'an urban area) within the Linan district, where 60% of Chinese hickory tree yields originate. The isolated cultures caused cankers on Chinese hickory tree branches, but infections did not occur on fruits or leaves under tested conditions. Combined morphological observations and phylogenetic analysis of multiple genes (ITS, ß-tubulin, and EF) indicated that five Botryosphaeriaceae species were recovered, including 89 isolates of Botryosphaeria dothidea, 4 isolates of Botryosphaeriaceae fabicerciana, 1 isolate of Botryosphaeriaceae qingyuanensis, 1 isolate of Botryosphaeriaceae corticis, and two isolates of Lasiodiplodia theobromae. B. dothidea was the most prevalent, and this is the first report of B. corticis, B. qingyuanensis, and L. theobromae infections in Chinese hickory trees. We investigated the mycelial growth, spore germination, and pathogenicity of these species at different temperatures. L. theobromae grew the fastest and B. cortices grew the slowest on potato dextrose agar. The optimum temperature of spore germination for all species was 30°C. L. theobromae was the most virulent species, followed by B. dothidea and B. qingyuanensis, then B. fabicerciana, and finally B. cortices. These new insights into fungal pathogen diversity provide critical new information to understand and manage tree trunk cankers of Chinese hickory.

[Mismatch repair protein expression of colorectal cancer: a retrospective analysis of 3 428 cases].

Objective: To analyze the expression of mismatch repair (MMR) proteins in colorectal cancers (CRC) and to evaluate the feasibility and potential pitfalls of immunohistochemistry (IHC) analysis for MMR. Methods: The IHC sections for MMR proteins were reviewed in 3 428 cases of resected CRC without neoadjuvant therapy at Tianjin Medical University Cancer Institute and Hospital from July 2014 to October 2018. For the cases with unclear MMR IHC results during the initial review, IHC staining was repeated and microsatellite instability (MSI) analysis was performed. Relationships between the expression of MMR proteins and MSI status as well as the clinicopathological parameters were analyzed. Results: IHC staining for MMR was repeated in 28 (0.8%) cases due to poor quality of original IHC sections. Inconsistent results between the original diagnosis and re-diagnosis were found in 119 (3.5%) cases, mainly resulting from PMS2 and MLH1. Finally, 261 (7.6%) cases of CRC showed mismatch repair deficiency (dMMR), mainly from the deficiency of both MLH1 and PMS2 (43.3%,113/261). In the 14 cases with MSI results, the concordant of MSI and MMR was 13 cases. In the 29 dMMR cases with next generation sequencing (NGS) results, the concordant of MSI-high and dMMR was 93.1%(27/29). The cases with inconsistent results between MSI and MMR showed negative expression of MSH6 or PMS2. Twenty-one CRC showed negative expression of MLH1 and partially positive (or weak positive) expression of PMS2, or negative expression of MSH2 and partially positive (or weak positive) expression of MSH6. Among the 19 cases with MSI results, 16 cases were MSI-high, two cases were MSI-low, and one case was microsatellite stable. Compared with mismatch repair proficiency (pMMR), dMMR was more frequently detected in female patients younger than 50 years old, with family history, at early stage (Ⅰ-Ⅱ) CRC, and in the tumors from right colon,with poor differentiation, or mucinous adenocarcinoma/signet ring cell carcinoma (all P<0.05). Conclusions: At present, IHC staining is a clinically effective and convenient method to detect MMR expression, but the operating process and result assessment remain variable and need to be standardized. MSI analysis can be performed in the difficult-to-evaluate cases for MMR to enhance prognostic evaluation and treatment option.

[The early and midterm results of coronary endarterectomy combined with coronary artery bypass grafting for diffuse coronary artery stenosis].

Objective: To examine the early and mid-term results of coronary endarterectomy (CE) combined with coronary artery bypass grafting (CABG) in the treatment of diffuse coronary artery stenosis. Methods: The clinical data and follow-up results of 248 patients who underwent CE+CABG surgery from January 2010 to January 2019 at Department of Cardiovascular Surgery, Nanjing Hospital Affiliated to Nanjing Medical University was analyzed retrospectively. There were 201 males and 47 females, aged (65.6±8.5) years (range: 43 to 79 years). The on-pump group included 156 patients and the off-pump group included 92 patients. CABG was performed after CE. CE was performed on 248 patients who represented 269 target coronary lesions, of which 108 were located on the left anterior descending artery and sub-branches, 140 were located on the right coronary artery and sub-branches, and 21 were located on the left circumflex artery and obtuse marginal artery. A total of 872 bypass grafts were performed, including 248 left internal thoracic arteries, 48 radial arteries, and 576 great saphenous veins, with (3.5±0.8) grafts (range:2 to 6 grafts) per patient.The grafts had satisfactory bridge blood flow after CE, with the graft flow rates of (26±8) ml/min (range: 13 to 59 ml/min) and the pulsatility index value of 3.1±0.8 (range: 2.0 to 6.7). The t test and χ2 test was used to compare the surgical results and graft patency rate between patients in on-pump and off-pump group, respectively. Results: The number of graft vessels of on-pump group and off-pump group was 3.6±0.9 and 3.2±0.7, respectively(t=1.637, P=0.085). There were 3 deaths during the perioperative period, with a mortality rate of 1.2%. Two people died of renal failure, and one case was due to postoperative refractory low cardiac output. Perioperative myocardial infarction occurred in 9 cases. The follow-up time was (41.8±21.4) months (range:1 to 68 months). The all graft patency rate was 78.4%(812/232) in 1 year and 69.8%(162/232) in 3 years postoperatively. The left coronary graft patency rate was significantly higher than the right coronary graft patency rate(1-year: 87.4% vs.73.1%, χ²=6.533, P=0.011, 3-year: 78.2% vs. 64.8%, χ²=4.588, P=0.032). There was no significant difference in graft patency rates between the on-pump group and off-pump group (1-year: 80.0% vs. 76.9%, χ²=0.277, P=0.599, 3-year:71.5% vs. 67.9%, χ²=0.300, P=0.584). Conclusions: CE+CABG is a safe and feasible technique for patients with diffuse coronary artery disease to get more satisfied complete revascularization, with good early and medium-term results and graft patency rates. The outcomes of on-pump or off-pump CE+CABG are similar.

[Distribution of the anterior corneal astigmatism in over 140 000 patients with age-related cataract].

Objective: To analyze the distribution characteristics of the anterior corneal astigmatism in 140 000 cataract patients from 18 hospitals in China. Methods: Retrospective study. A total of 143 889 patients (143 889 right eyes) over the age of 40 years with age-related catarac were admitted to 18 Aier eye hospitals in China from July 2015 to October 2018. The average values of the three measurements of the magnitude of anterior corneal astigmatism, the meridian of corneal astigmatism, anterior chamber depth, corneal refractive power, and axial length measured by IOLMaster 500 were obtained. The data acquisition method of each sub-center was to collect and analyze the electronic case data in accordance with the inclusion and exclusion criteria, and to provide them for the sponsor Wuhan Aier Eye Hospital. Non-normal distribution data are presented as M (P25, P75). Mann-Whitney test, Kruskal-Wallis test, Chi-square test were used to analyze the distribution differences of the magnitude of corneal astigmatism and the meridian of corneal astigmatism in gender, age, anterior chamber depth, corneal refractive power and axial length. Results: Among the 143 889 patients, 84 319 were females and 59 570 were males, the median age was 72 (65, 78) years old, the median corneal astigmatism was 0.84 (0.51, 1.33) D; the corneal astigmatism was ≥0.75 D in 80 895 patients (56.22%) and was ≥1.00 D in 57 304 patients (39.83%). The median corneal astigmatism was 0.87 (0.53, 1.37) D in women and 0.82 (0.50, 1.29) D in men; with statistical difference (U=-14.891; P<0.05). The proportion of with-the-rule (WTR) astigmatism was 33.26% (28 046/84 319) for women and 34.26% (20 408/59 570) for men; The proportion of against-the-rule (ATR) astigmatism was 49.08% (41 385/84 319) for women and 46.91% (27 945/59 570) for men, with statistical difference (χ²=70.913; P<0.05). With the increase of age, the magnitude of corneal astigmatism first decreased from 0.94 (0.57, 1.48) D to 0.75 (0.46, 1.18) D, and then increased to 1.19 (0.74, 1.79) D, with statistical difference (H=1 263.438; P<0.05), and the change was at 61 to 70 years old. With the increase of age, the proportion of WTR astigmatism decreased from 77.50% (396/511) to 12.50% (3/24), the proportion of ATR astigmatism increased from 11.15% (57/511) to 79.07% (34/43), and the proportion of oblique astigmatism changed little from 17.02% (16/94) to 19.92% (245/1 230), the distribution difference was significant (χ²=10 174.496; P<0.05). As the anterior chamber became shallow, the magnitude of corneal astigmatism significantly increased from 0.82 (0.51, 1.31) D to 1.05 (0.61, 1.56) D, and the proportion of ATR astigmatism increased from 47.32% (60 207/127 227) to 51.69% (184/356) (H=409.961, χ²=120.995, both P<0.05). With the corneal refractive power rising, the magnitude of corneal astigmatism increased from 0.80 (0.49, 1.33) D to 0.95 (0.58, 1.53) D, the proportion of ATR astigmatism decreased from 52.84% (4 963/9 392) to 39.97% (9 023/22 577); the difference was significant (H=808.562, χ²=752.147, both P<0.05). When the axial length was>25.00 mm, the magnitude of corneal astigmatism was highest [1.04 (0.62, 1.65) D], and the proportion of ATR astigmatism was also highest [49.00% (10 964/22 376)]; the difference was significant (H=2 071.198, χ²=131.130, all P<0.05). Conclusions: The meridian of corneal astigmatism in middle-aged and elderly cataract patients is mainly ATR astigmatism. With the increasing of age, the magnitude of corneal astigmatism decreases first and then increases. The turning point from the proportion of WTR astigmatism to the proportion of ATR astigmatism is 65 years old. The shallower the anterior chamber is, the more the magnitude of corneal astigmatism and the proportion of ATR astigmatism increase. When the axial length is>25.00 mm, both the magnitude of corneal astigmatism and the proportion of ATR astigmatism reach the peak. (Chin J Ophthalmol, 2021, 57: 56-62).

LncRNA DSCAM-AS1 promotes non-small cell lung cancer progression via regulating miR-577/HMGB1 axis.

Non-small cell lung cancer (NSCLC) is a major source of cancer mortality. Long non-coding RNA DSCAM-AS1 has been certified to be involved in the pathogenesis of NSCLC. This study aimed to further investigate the potential mechanism of DSCAM-AS1 in NSCLC progression. The expressions of DSCAM-AS1, miR-577, and high mobility group box 1 (HMGB1) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay. Cell viability was assessed by Cell Counting Kit-8 (CCK-8) assay. Flow cytometry assay was conducted to monitor cell apoptosis. Cell migration and invasion were measured by transwell assay. Wnt/ß-catenin pathway-related factors were detected by western blot assay. The relationship between DSCAM-AS1, miR-577, and HMGB1 was validated by bioinformatics analysis and dual-luciferase reporter assay. The xenograft mouse model was established to analyze tumor growth in vivo. DSCAM-AS1 and HMGB1 were upregulated, while miR-577 was downregulated in NSCLC tissues and cells. DSCAM-AS1 promoted cell proliferation, migration and invasion, and restrained cell apoptosis in NSCLC cells. Overexpression of HMGB1 reversed the effects of DSCAM-AS1 depletion on the progression of NSCLC. DSCAM-AS1 modulated HMGB1 expression by sponging miR-577. DSCAM-AS1 regulated the Wnt/ß-catenin pathway by regulating miR-577 and HMGB1. DSCAM-AS1 knockdown blocked the tumor growth in vivo. In conclusion, DSCAM-AS1 facilitated NSCLC progression by regulating the HMGB1-mediated Wnt/ß-catenin pathway, providing a promising therapeutic target for NSCLC.

Hypoxia-responsive miR-346 promotes proliferation, migration, and invasion of renal cell carcinoma cells via targeting NDRG2.

Renal cell carcinoma (RCC) is the most common malignant tumor of the kidney. In this study, we investigated the role of miR-346 in RCC cells under hypoxia. OS-RC-2 and 786-O cells were cultured in 1% O2 or normal oxygen. Cell proliferation, migration, and invasion abilities were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, transwell migration, and invasion assays, respectively. Quantitative real-time PCR (qRT-PCR) was performed to detect the expression of miR-346 and N-myc downstream-regulated gene 2 (NDRG2). Then bioinformatics analysis, dual-luciferase reporter assay, and RNA immunoprecipitation were carried out to determine the relationship between miR-346 and NDRG2. The protein expression of NDRG2 was detected by western blot assay. Hypoxia promoted cell proliferation, migration, and invasion in OS-RC-2 and 786-O cells. Meanwhile, we found that miR-346 was upregulated in RCC cells under hypoxia as relative to normoxia. miR-346 deletion could decrease the viability, migration, and invasion abilities of RCC cells under hypoxia. Besides, our data demonstrated that NDRG2 was a target gene of miR-346. The expression of NDRG2 in OS-RC-2 and 786-O cells was lower under hypoxia than under normal oxygen conditions. Moreover, NDRG2 overexpression could inhibit cell proliferation, migration, and invasion in RCC cells under hypoxia. And NDRG2 silencing reversed the inhibitory effects of the miR-346 inhibitor on the viability, migration, and invasion abilities of RCC cells in hypoxia conditions. miR-346 promoted the viability, migration, and invasion of RCC cells under hypoxia by targeting NDRG2.